A major obstacle to AIDS vaccine and therapeutic development is the incomplete understanding of what constitutes protective immunity to HIV-1. In order to understand the role of humoral immunity in preventing HIV infection, we are studying antibody neutralization of HIV-1. Using both polyclonal and monoclonal antibodies we are analyzing the sensitivity patterns of a variety of primary and laboratory virus isolates. Neutralizing antibody activity is being measured both on autologous and heterologous virus isolates to investigate the prevalence neutralization resistance. We are finding that the ability to neutralize HIV depends not only on the antibody repertoire of an individual but also on the phenotype of HIV which is growing in the patient. These HIV neutralization resistance and susceptibility patterns are being genetically mapped using chimeric HIV strains constructed using a patient's viral envelope amino acid sequence substituted into a known viral background and then tested for antibody sensitivity. Assays with monoclonal antibodies and type specific antisera should provide methods to immunotype patient isolates and to evaluate humoral responses to HIV vaccine candidates in clinical trials.